1. The Medical Research Council (MRC) is
the UK's leading publicly-funded body charged with supporting
and encouraging medical research for the improvement of human
health. It welcomes the opportunity of responding to the International
Development Committee's inquiry, and more specifically to address
point 2(d) concerning the response of the international community.
The other points highlighted in the Committee's notice are essentially
beyond the MRC's remit.

2. The MRC has a significant and well-established
portfolio of research relating to HIV/AIDS. At the same time,
the MRC supports a significant amount of research relevant to
developing societies, much of this specifically concerning HIV/AIDS.
During 1998, the MRC considered its role in supporting research
relevant to developing societies. It was agreed that the existing
strategic investments in Africa (see below) continued to be of
major importance scientifically and in relation to the MRC's overall
mission to improve human health. Continued close interaction with
DFID was encouragedthe current Concordat between the MRC
and DFID covers the period 1998-2003, and DFID financially contributes
to the MRC's work in developing countries.

3. It is notable that, whilst the predicted
AIDS epidemic in the Western world has never reached the size
initially feared, the disease is now one of the major causes of
adult mortality in many countries in the developing world, especially
in sub-Saharan Africa. The MRC's strategy in confronting this
problem is essentially threefold:

 fundamental research into aspects
of HIV/AIDS;

 research into prevention and public
health;

 vaccine research (important for developing
countries because of the high costs of drug therapy).

Reflecting this approach, there are three major
MRC programmes that will be of interest to the Committee, since
they each represent a commitment to confront the impact of HIV/AIDS
in an African context. It is noteworthy that the programmes are
tailored to offer health solutions that reflect the needs of the
host societies.

MRC/UGANDA VIRUS
RESEARCH INSTITUTE
PROGRAMMEON
AIDS IN UGANDA

4. The MRC/Uganda Virus Research Institute
(UVRI) Programme on AIDS in Uganda was established in 1988, as
an integrated multidisciplinary research programme for the study
of HIV-1 in Uganda. Professor Jimmy Whitworth has led this since
1995. As part of the 1998 review of the programme, the MRC agreed
a five-year funding plan worth over £7.4 million.

5. Importantly, the programme of research
in Uganda is multidisciplinary. It combines social science, epidemiology,
statistics, clinical medicine, virology and immunology, and is
supplemented by work in health promotion. The factors determining
transmission of HIV infection and subsequent disease progression
are being studied in two rural population cohorts, and a major
intervention trial of behaviour change and improved management
of sexually transmitted diseases will be completed by the end
of this year. The future plans include expansion of the ongoing
cohort studies and the development of further cohorts for secondary
intervention studies and potential virucide and/or vaccine trials.

6. Moreover, the very substantial benefits
of investment in basic researchin terms of the development
of new (but expensive) therapieshave thus far had very
little impact on the overall course of the epidemic in the developing
world. The picture in Uganda does appear to be slightly more optimistic.
Over a 10-year period, there has been a significant fall in the
prevalence and incidence of HIV in the adult cohort of the MRC/UVRI
Programme. Overall adult prevalence has declined from 8.2 per
cent in 1989-90 to 6.6 per cent in 1998-99. The greatest decline
has been mostly in young men aged 20-24 and young women aged 13-24
years. The incidence of new infection has also dropped significantly,
from 7.6 per 1,000 person years at risk in 1990 to 3.2 per 1,000
person years at risk. This is the first evidence from Africa of
falling HIV prevalence and incidence in general populations. The
results of the research supported by MRC have contributed significantly
to Uganda Government health policy and strategy development on
the control of the epidemic.

MRC LABORATORIES,
THE GAMBIA

7. The MRC Laboratory currently runs eight
programmes of research relevant to the health of developing societies.
These span HIV/AIDS, tuberculosis, malaria, reproductive health,
viral diseases, respiratory infections and non-communicable diseases.
In addition, the Laboratory co-ordinates a number of clinical
trials, behavioural intervention programmes and maintains important
cohorts.

8. The Laboratory represent a major investment.
At its last review of the facility in 1997, the MRC approved research
proposals with a value of £21.7 million over a five-year
period. The Laboratory has 600 staff and runs four field stations,
and has a very close and fruitful working relationship with the
Gambia Government Department of State for Health.

9. The prevalence of HIV infection is still
lower in West Africa than in other parts of the continent, but
while the HIV-2 epidemic remains stable, the incidence of HIV-1
is increasing. The main aim of the Laboratory's research in HIV/AIDS
is to gain an understanding of the differences between HIV-1 and
HIV-2 in their natural history and pathogenesis. The most striking
differences between the infections occur in the asymptomatic phase,
which in HIV-2 is prolonged and characterised by a low level viraemia,
low transmission rates and a low mortality. A few HIV-2 infected
individuals, who are infected with a more pathogenic virus or
are genetically susceptible, die rapidly. The opposite is true
of HIV-1, which rapidly kills most of those infected. These differences
are being related to the molecular biology of the two viruses
and their recognition by the host's immune system.

10. The Laboratory's research effort in
HIV/AIDS is based on three broad approaches:

 clinical studies, made largely possible
thanks to the Laboratory's genito-urinary clinicthe MRC
is the national referral centre for HIV care in The Gambia;

 community studies, notably HIV-2
studies in a rural area of neighbouring Guinea-Bissau and the
study of mother to child transmission of HIV-1 and HIV-2 in The
Gambia; and

 laboratory studies of cytotoxic T
lymphocytes and viral load in the two infections.

MRC HUMAN IMMUNOLOGY
UNIT

11. In 1998, the MRC committed almost £6
million over five years to set up the Human Immunology Unit at
Oxford University. It was established to formally bring together
groups working in different disciplines in immunology, with Professor
Andrew McMichael as the Director. He guides a number of programmes
of research that comprise a multidisciplinary approach to understanding
the human immune response and its role in disease processes.

12. The Unit is initially focusing on infectious
diseases, especially HIV infection. Programmes of research going
on at the Unit notably include the preparation for, and trials
of, HIV vaccines in the UK and Kenya. Others are: AIDS disease
progression; characterisation of HIV specific immune responses;
and HIV the role of breast feeding in infection of infants.

13. There is currently renewed interest
in vaccines against HIV. Almost 20 years of research has failed
to produce an effective vaccine. Professor McMichael's research
suggests that one reason for this might be the slow arrival of
a particular type of immune cells called Cytotoxic T Lymphocytes
(CTLs) that destroy virus containing cells. New viruses are therefore
produced and released before the body's natural defences can kill
the original invaders. If a vaccine could boost the production
of CTLs, the body might be able to protect itself against HIV
infection. It is known that different types of vaccine stimulate
different parts of the immune response. The approach being taken
at the MRC Human Immunology Unit is to use a combination of vaccines
to target particular responses.

14. As a complement to MRC investments,
Professor McMichael has received funding from the International
AIDS Vaccine Initiative (IAVI) to begin a trial testing for an
HIV vaccine, in collaboration with the University of Nairobi.
The trial is a combination of a naked DNA vaccine plus a modified
Vaccinia Ankara (MVA) virus vaccine. There is encouraging data
that this approach might work in the long term. Therapeutic vaccinesto
stimulate the immune system in individuals that are already infectedare
also of interest for AIDS treatment. For example, the potential
exists for using anti-retroviral drugs to decrease HIV load and
then vaccination to boost the immune system to eliminate the virus
completely. In addition, because there are many common mechanisms
that exist between diseases such as AIDS, Malaria, TB, Cancer
and autoimmune diseases, this research has wider implications
for public health.

15. The first phase of the trial, currently
scheduled to begin in August this year, involves testing on a
small number of low-risk volunteers in the UK. Phase one will
be repeated in Kenya on a similarly small scale, under the direction
of Dr J J Bwayo of the Department of Medical Microbiology at the
University of Nairobi; subject to local ethics committee approval,
this is expected to start in December. Pending a successful outcome,
phase two of the trial would take place in Kenya, targeting those
at high risk, such as prostitutes in Nairobi. The intention would
be to accompany the trial with high quality nursing and social
service support. Phase threethe final stagewould
be a trial of people at normal risk, possibly in rural Kenya.